title: Expression of Epidermal Growth Factor Receptor Detected by Cetuximab Indicates Its Efficacy to Inhibit In Vitro and In Vivo Proliferation of Colorectal Cancer Cells.
abstract: Cetuximab is a chimeric mouse-human monoclonal antibody that targets the human epidermal growth factor receptor (EGFR). However, EGFR expression determined by immunohistochemistry does not predict clinical outcomes of colorectal cancer (CRC) patients treated with cetuximab. Therefore, we evaluated the correlation between EGFR levels detected by cetuximab and drug sensitivities of CRC cell lines (Caco-2, WiDR, SW480, and HCT116) and the A431 epidermoid carcinoma cell line. We used flow cytometry (FCM) to detect EGFR-binding of biotinylated cetuximab on the cell surface. Subcloned cell lines showing the highest and lowest EGFR expression levels were chosen for further study. Cytotoxic assays were used to determine differential responses to cetuximab. Xenograft models treated with cetuximab intraperitoneally to assess sensitivity to cetuximab. Strong responses to cetuximab were specifically exhibited by subcloned cells with high EGFR expression levels. Furthermore, cetuximab inhibited the growth of tumors in xenograft models with high or low EGFR expression levels by 35% and 10%-20%, respectively. We conclude that detection of EGFR expression by cetuximab promises to provide a novel, sensitive, and specific method for predicting the sensitivity of CRC to cetuximab.
authors.affiliation: Keio University, School of Medicine, Department of Surgery, Shinjuku-ku, Tokyo, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Shigeta
authors.forename: Tetsu
authors.initials: T
authors.lastname: Hayashida
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hoshino
authors.forename: Koji
authors.initials: K
authors.lastname: Okabayashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Endo
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ishii
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitagawa
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D000068818:Cetuximab / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000473:pathology*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D051379:Mice; D023041:Xenograft Model Antitumor Assays
chemical_list: D066246:ErbB Receptors; D000068818:Cetuximab